The data from 23andme is quite interesting and may play in well with what is going on in terms of current research. I believe that it would be important to take a closer look at this data and would like to ask all members with results from 23andme to please contact me via pm.
Thanks.
Awor
yasko has said you have to treat CBS first or else others wonāt work. is anyone else treating CBS? if so please PM meā¦
Its been 9 months since this thread started. Is there anyone who has followed this protocol for at least 3 months and can report any changes in their symptoms?
Yes i have. My changes :
On the plus side :
-Libido back although time required to achieve erection is high.
-More eligible to remember dreams
-Sleeping through the night
-Psychological problems gone. More extroversion
On the minus side
-Possibly positive : (will have to confirm in about 15 days after a blood test):
-Decreased homocysteine (appeared normal towards the high range in a previous test but i had no previous test reference)
-Better thyroid function
-Better Free Testosterone (on the last test appeared low-normal - used to be below normal levels but i need to see the progression )
Please note that the benefit i saw was from NAC supplementation although some people in the forum had a bad reaction to it - perhaps due to CBS, SUOX mutations. I decided to perform the complete methylation regimen (as Droit suggested) in order to see whether the Negatives i described above will resolve. I take NAC 1000mg per day (600mg morning+400 mg evening)
Notice also that Glutathione (which is boosted with NAC) is an important product of the methylation cycle.
I am waiting for 23andme results and i will share them with the community and also send them to the admins.
Wow!!! All this stuff fits exactly into my theory!! You guys are addressing what I believe to be a result of an imbalanced progesteone receptor in favor of estrogen!!
ncbi.nlm.nih.gov/m/pubmed/18692819/
Here is another study showing oxidative stress may be regulated by the amount of progesterone in the brain!! Guys this has to be it!! I feel like promoting the meythlation cycle is dealing with the affects of what the underlying condition is, which is an imbalanced progesteone receptor leading towards poor gene expression (unopposed estrogen)
Damn guys, I think we found the holly grail of the condition. Here is more:
frontiersin.org/neuroendocri ā¦ 00010/full
endo.endojournals.org/content/ea ā¦ 9.full.pdf
Hi Finatruth,
In my 2-year involvement on trying to figure out what causes PFS, one of my hypotheses were about Cytochrome P450scc.
I think the chain goes like this : Cholesterol ->Pregnenolone->Progesterone
I felt much better whenever i ate high-cholesterol foods : It would boost my libido in a matter of hours.
So i had a look down that route and found about P450scc. From my notes :
I tried Ginger Root (but not L-Carnitine) without any luck, however i would like to know more about your theory. My question is : What can we do in order to try this out?
Finatruth,
The impact of a halted Methylation Cycle is massive. The most alluring aspect of this theory is the explanation of how you get to PFS, how it describes our symptoms and how it is persistent:
Get from Finasteride to a Methylation Block
The accumulation of these effects overcomes your glutathione stores.
How itās persistent:
An explanation of our symptoms
From there, in a persistent state of oxidative stress, reduced glutathione and a halted methylation cycle you can get all of these peripheral things you and others have posted on.
So far weāve had 100% alignment with this theory in test results, but only a handful of data points. Anyone interested should get the Methylation Pathways Panel from Vitamin Diagnostics which will directly tell you if you are in this state.
hdri-usa.com/tests/methylation/
europeanlaboratory.nl/
This thread is meant to be an inversion of the typical āsupplement now to prove the theoryā patterns typically found on the board. If we can get a dozen of these showing consistent results, I think that will drive focus into this area and exploring what flavor of the Methylation Protocol works best for us.
The Curcumin Analog ca27 Down-Regulates Androgen Receptor Through an Oxidative Stress Mediated Mechanism in Human Prostate Cancer Cells, ncbi.nlm.nih.gov/pmc/articles/PMC3309160/
NOVEL MECHANISMS OF ANDROGEN RECEPTOR DEGRADATION BY ALPHA-TOCOPHERYLQUINONE AND CURCUMIN ANALOG 27, repository.unm.edu/bitstream/ha ā¦ sequence=1
viewtopic.php?f=27&t=7178&p=71331&hilit=Androgen+methylation#p71331
Effect of dihydrotestosterone on mouse embryonic stem cells exposed to H2O2-induced oxidative stress, ncbi.nlm.nih.gov/pmc/articles/PMC2811836/
viewtopic.php?f=27&t=7178&p=70973&hilit=allopregnanolone#p70973
Androgen receptor signaling induced by supraphysiological doses of dihydrotestosterone in human peripheral blood lymphocytes, onlinelibrary.wiley.com/doi/10.1 ā¦ ated=false
Mechanisms for redox actions of nicotine and glutathione in cell culture, relevant to periodontitis, ncbi.nlm.nih.gov/pmc/article ā¦ po=34.0909
Droit- I think we are saying the same things. I believe based on the studies I have posted where they purposefully use Finasteride to destroy, abolish, wipe away progesterone in cells, caled a PR (Progesterone Receptor) knockout. From there everything is affected/downregulated. By the way the progesterone receptor is located right near the AR.
So if this is all true, what would be a hypothetical treatment protocol, If the methylation cycle is blocked? Again, I think the limited success with this treatment so far indicates that it defintely is whats involved but not the root cause. I have had enromous gains in the last month from excessive alcohol intoxication. My libido is almost pre-fin, I am waking up extremely horny almost every day. My hair and body is itching like crazy, including eyebrows and I am getting a huge increase in sexual thoughts, desire, and function. I believe the increase in progesterone/allo is responsible. Many other have noted this upswing phenomenon. Lastly, check out how many guys got rock solid erections while flying. Once again, I beleive based on studies that high altitudes increase progesterone levels in the brain.
Is there room in this theory for why someone like me would get some initial, dramatic results with T injections? My libido and erection strength were fully restored the first time I had a shot ā it was pretty amazing. But the improvement was uneven ā some days it would all be back, some days Iād be dead ā and it leveled off to baseline after a few weeks and hasnāt been back since.
Finatruth,
Thank you again for your continued research in this area. It is a real value you having your attention here. I think your research on progesterone receptor is great and your commitment to neurosteroids is going to be important to the whole community.
The focal point of this thread is: PFS is rooted in high oxidative stress that causes a persistent halted methylation cycle. Your finding that progesterone is important in handling oxidative stress is yet another thing we can piling on the heap of the protection standpoint. But I do think the progesterone angle is a separate thread.
Remember, This thread is meant to be an inversion treatment guided verification of hypothesis. We have to show that a majority of people are in this state, then work with practitioners to find the best treatment plan.
From the classical Methylation Protocol: those who have done the protocol correctly as we know it and stuck with it have gotten the most honest, consistent and persistent gains Iāve seen on this board. And I think we understand why we are getting gains. The lack of total recoveries does not speak to a disproven hypothesis.
As Iāve posted: I have taken two methylation panels. My numbers have improved, but not into range.
viewtopic.php?f=27&t=7178&p=70956&hilit=range#p70956
If I were able to get my lab values into normal range and I wasnāt on my way out, then Iād start to look at things differently.
So again, my philosophy in this thread is that treatment first doesnāt tell us anything specific.
For example: You are getting gains from alcohol consumption. Why is that? It could be progesterone related, but its more likely that youāre just jacking up your dopamine temporally. I think this is haphazard and youāre probably just causing more oxidative stress and at some point your just going to reduce your dopamine receptors.
Another example of treatment first creating a muddled understanding is the āsulforaphaneā protocol being carried out here:
viewtopic.php?f=27&t=7189&start=20#p71871
From what I can tell, the intent was to test an epigenetic modulator so someone did a trial of a product with āsulforaphaneā and reported improvement. People probably think this confirms that epigenetics are in play.
But it turns out, while sulforaphane may be a weak broad spectrum epigenetic modulator, it overwhelming is used to raise glutathione.
plosone.org/article/info%3Ad ā¦ ne.0066407
Further, in the trial linked supporting this theory:
clinicaltrials.gov/ct2/show/NCT0 ā¦ ane&rank=3
They are explicitly looking at glutathione and Nrf2, both markers of oxidative stress.
So what does the outcome of the sulforaphane trial tell us? I donāt think it tells us anything. It would have been nice to see a Methylation Panel before an after the trial, which I suspect we would have seen no change in the methylation cycle metabolites, but improved glutathione.
Testing is the only way to determine the root cause. Treatments can be developed in response.
think the PR receptor is a bigger deal than you think. Here is a recent study at the university of Tulane 2013, most signficantly āInhibition of 5ARI additionally influences progesterone and deoxycorticosterone levels and may alter psychological functions, including increased depression, melancholy and loss of general well being. Ejaculatory dysfunction has not been well studied in patients using 5ARā
Could some of them post what gains they have experienced? Iāve read about marioās, but I canāt find gains for anyone else. I keep asking. Iād really like to know how it is helping people. Itās entirely possibly Iām missing it, my fog has gotten worse lately. Sorry. 
Iām going to give tribulus a run soon, but after that Iām going to buckle down on this protocol I think. Iāll post my experience.
Ok, thank you very much. Sorry again, this fog is getting bad.
Has anyone been on a tetracycline antibiotic AFTER they got PFS?
I ask because tetracyclines up-regulate 5ar in the brain and therefore should increase 5ar metabolites.
I am posting the 23AndMe Methylation Cycle related data.
The format is in number of mutations (different from āwild typeā). A 1 means the person is heterozygous for a mutation, and a 2 means homozygous for a mutation.
We donāt have to dataset to run formal statistics yet, but the challenge with something like this is that you donāt need any one mutation to have a debilitated methylation capacity. It is the combination of events that makes things more sever. For example: everyone has
or
The short-coursers seem to have MTHFR, BHMT and CBS. We will have to think about what statistics we will need to express this with larger data.
Looks like 100% has tested for mutation on VDR-TAQ.
This can cause major dopamine disruptions.
Moonman have you ever tried Ginkgo biloba? Do you feel better with vitamin D?
I suspect I have low dopamine. One of my lingering sides is it takes a long time for me to orgasm despite good erections.
Viamin D is def. one of my staples. There is a noticeable effect from when I do and do not take it. I took Ginko way back when I was originally taking SP before my crash, but have not since.
pfsfoundation.org/news/abstr ā¦ -in-italy/
Based on these and other results, we are currently testing a number of novel therapeutic approaches to counter finasteride-induced depressive effects and explain its antidopaminergic actions.
Btw, I am not saying that the VDR-TAQ mutation are the cause of our dopamine issues, but none the less it is something we as a board could look into further. I believe the COM-T and other methylation genes have major play on D as well.